Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.
Fiche publication
Date publication
janvier 2015
Journal
PloS one
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WEBER Mickaël
Tous les auteurs :
Brieño-Enríquez MA, García-López J, Cárdenas DB, Guibert S, Cleroux E, Děd L, Hourcade Jde D, Pěknicová J, Weber M, Del Mazo J
Lien Pubmed
Résumé
In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.
Mots clés
Animals, Apoptosis, Cell Differentiation, DNA Methylation, Endocrine Disruptors, toxicity, Environmental Pollutants, toxicity, Epigenesis, Genetic, drug effects, Female, Germ Cells, drug effects, Male, Mice, MicroRNAs, genetics, Oxazoles, toxicity, Positive Regulatory Domain I-Binding Factor 1, Pregnancy, Prenatal Exposure Delayed Effects, chemically induced, Testis, drug effects, Transcription Factors, genetics
Référence
PLoS ONE. 2015 ;10(4):e0124296